Stepwise Therapy Research Articles

Activatable “Matryoshka” nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer

Drug resistance is always a challenge in conquering breast cancer clinically. Recognition of drug resistance and enhancing the sensitivity of the tumor to chemotherapy is urgent. Herein, a dual-responsive multi-function “Matryoshka" nanosystem is designed, it activates in the tumor microenvironment, decomposes layer by layer, and release gene and drug in sequence. The cell is re-educated by NgBR siRNA first to regain the chemosensitivity through regulating the Akt pathway and inhibit ERα activation, then the drugs loaded in the core are controlled released to killing cells. Carbonized polymer dots are loaded into the nanosystem as an efficient bioimaging probe, due to the GE11 modification, the nanosystem can be a seeker to recognize and evaluate drug-resistance tumors by photoacoustic imaging. In the tumor-bearing mouse, the novel nanosystem firstly enhances the sensitivity to chemotherapy by knockdown NgBR, inducing a much higher reduction in NgBR up to 52.09%, then effectively inhibiting tumor growth by chemotherapy, tumor growth in nude mouse was inhibited by 70.22%. The nanosystem also can inhibit metastasis, prolong survival time, and evaluate tumor drug resistance by real-time imaging. Overall, based on regulating the key molecules of drug resistance, we created visualization nanotechnology and formatted new comprehensive plans with high bio-safety for tumor diagnosis and treatment, providing a personalized strategy to overcome drug resistance clinically.

Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review.

Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.

Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: The efficacy and durability of initial combination therapy for type 2 diabetes (EDICT).

To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin → glipizide → glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat. At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (P=.0006). Twenty-seven of 39 subjects (69%) receiving conventional therapy had grade 2/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (P=.0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (P=.04). Conventional therapy subjects had more liver fat (MRI-PDFF) than triple therapy (12.9% vs. 8.8%, P=.03). The severity of steatosis (CAP) (r=0.42, P < .001) and fibrosis (LSM) (r=-0.48, P < .001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS. At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis-4, and AST/ALT ratio) have limited value in predicting response to therapy.

Stepwise photothermal therapy and chemotherapy by composite scaffolds of gold nanoparticles, BP nanosheets and gelatin immobilized with doxorubicin-loaded thermosensitive liposomes.

In recent years, the synergistic effect of photothermal therapy (PTT) and chemotherapy has been recognized as an effective strategy for cancer treatment. Controlling the PTT temperature and drug release profile is desirable for minimizing the unexpected damage to normal cells. In this study, a smart platform of stepwise PTT and chemotherapy has been developed by using composite porous scaffolds of biodegradable black phosphorus (BP) nanosheets, gold nanorods(AuNRs), doxorubicin (Dox)-encapsulated thermosensitive liposomes and biodegradable polymers. Under near-infrared (NIR) laser irradiation, the composite scaffolds could attain high and low local temperatures before and after BP degradation, respectively. Dox release from the composite scaffolds could be controlled by the temperature change. In vitro cell culture and in vivo animal experiments indicated that a strong synergistic effect of PTT and chemotherapy could be achieved at an early stage of treatment before BP degradation, and a mild hyperthermia effect was shown for chemotherapy in the late stage after BP degradation. Moreover, the composite scaffolds after the complete release of Dox could support the proliferation of mesenchymal stem cells. The composite scaffolds showed a synergistic effect of stepwise PTT and chemotherapy for breast cancer elimination and promoted stem cell activities after killing cancer cells.

Arthroscopic Ischial Tuberoplasty: Treatment of Ischiofemoral Impingement

Background: Ischiofemoral impingement is a rare but increasingly recognized as a source of hip pain. Its etiology is often multifactorial and can be due to congenital, iatrogenic, or extra-articular pathology. Prior literature has described lesser trochanter osteoplasty and iliopsoas release for the treatment of ischiofemoral impingement, but postoperative hip flexor weakness has been noted with this technique. We present a novel technique for the treatment of ischiofemoral impingement, with resection of the ischial tuberosity. Indications: Patients with ischiofemoral impingement that remain symptomatic despite nonsurgical management, or patients with persistent gait abnormalities, are considered for surgery. Technique Description: In the prone position, direct posterior and posterolateral arthroscopic portals are created in the gluteal fold. The posterior femoral cutaneous and sciatic nerve are identified. Fluoroscopy is used to identify the region of impingement on the ischial tuberosity and the overlying hamstring tendon is elevated off the tuberosity. An arthroscopic burr is used to resect the tuberosity. Fluoroscopy is utilized to confirm adequate resection. This is combined with a dynamic examination under direct arthroscopic visualization with the hip in an extended, adducted, and externally rotated position. To repair the hamstring tendon, 2 double-loaded anchors are placed into the ischium, the sutures of which are used to repair the hamstring tendons using a horizontal mattress configuration. Patients undergo a stepwise postoperative physical therapy protocol, followed by a functional testing profile prior to return to competitive sport. Results: Significant improvements in patient-reported outcomes have been reported following treatment of ischiofemoral impingement, with some studies reporting Hip Outcome Score—Activities of Daily Living (HOS-ADL) &gt;90 at 2 years postoperatively. Athletes have been able to return to sport at a mean 5.6 months after surgery. Large studies have yet to report on outcomes compared with nonsurgical or open techniques. Discussion/Conclusion: Recent advancements in endoscopic techniques have allowed for adequate visualization and release of ischiofemoral impingement. We present our endoscopic technique of ischial tuberoplasty, which, compared to lesser trochanter osteoplasty and iliopsoas release, may reduce the incidence of postoperative hip flexor weakness.

Efficacy and Safety of a Fixed Combination of Glycyrrhizic Acid and Essential Phospholipids in Non-Alcoholic Fatty and Alcoholic Liver Disease: Results from Randomized Placebo-Controlled Trials

Background. Drug treatment of non-alcoholic fatty and alcoholic liver disease remains an urgent, unsolved problem. Due to the commonality of many pathogenetic mechanisms and predictors of progression, a universal approach to the search for a therapeutic agent can be considered.&#x0D; Aims pooled analysis of the results of two multicenter, randomized, double-blind, placebo-controlled studies of a fixed combination of glycyrrhizic acid and essential phospholipids in two dosage forms to study its efficacy and safety in non-alcoholic fatty and alcoholic liver disease, in the presence and absence of predictors of disease progression.&#x0D; Methods. The pooled analysis included 180 patients with non-alcoholic fatty liver disease (Gepard study) and 120 patients with alcoholic liver disease (Jaguar study). Patients of the main group received a fixed combination of 5.0 g intravenous jet 3 times a week for the first 2 weeks; then 2 capsules 3 times a day for the next 10 weeks. Patients in the control group received placebo according to the same scheme. The total duration of treatment was 12 weeks in the Gepard study (1 course of stepwise therapy) and 24 weeks in the Jaguar study (2 courses of stepwise therapy). A comparative analysis of the efficacy and safety of a fixed combination and a placebo was carried out, in the presence and absence of predictors of progression, separately for each nosology and in a mixed sample.&#x0D; Results. In patients with non-alcoholic fatty and alcoholic liver disease who received the fixed combination, in contrast to the placebo group, there was a statistically more significant decrease in the level of biochemical markers of inflammation alanine aminotransferase, aspartate aminotransferase, adiponectin, and the value of the AktiTest index. There was no negative trend in the NAFLD fibrosis score; more significant positive dynamics of FibroTest is shown. Predictors of disease progression hyperglycemia, hyperlipidemia, age did not have a negative impact on the results in the study group. The efficacy of the study drug was noted in patients with non-alcoholic fatty liver disease and normal body weight; data were obtained indicating its possible effectiveness with a high activity of the inflammatory process associated with alcoholic liver damage. The frequency of adverse events in the study and control groups was comparable.&#x0D; Conclusions. Based on a generalized analysis of the results of two studies, promising directions for the study and use of a fixed combination of glycyrrhizic acid and essential phospholipids were identified: non-alcoholic fatty liver disease without obesity, alcoholic steatohepatitis of high activity (as an adjuvant); steatohepatitis of non-alcoholic and alcoholic etiology, combined with hyperglycemia and hyperlipidemia.

Rational pharmacotherapy in modern gastroenterology

Abstract Introduction. Modern gastroenterology is characterized by the combined (comorbid) nature of the diseases. In treatment, this promotes polypharmacy and increases complications (drug lesions, allergic reactions, exacerbation of diseases of other organs and systems), and, importantly, increases the cost of pharmacotherapy.Aim. To compare two pharmacotherapy options for patients with gallstone disease at the stage of biliary sludge and patients with biliary sludge combined with irritable bowel syndrome.Materials and methods. In the work, based on the experience of treating 170 patients, two options for pharmacotherapy are considered, which may well turn out to be rational in all respects. Option 1 - monotherapy aimed at one of the components that form a complex pathogenetic symptom complex. The basis for offering this treatment option is the biological concept of the “regulatory cascade”. Option 2 – “stepwise” (stepwise) therapy with the choice of the “base” drug for the first step. Evaluation of the effectiveness and rational correction for the second step of treatment and subsequent ones – if necessary. Results. The biliary sludge was eliminated or reduced in patients who received the UDCA monotherapy against the background of recovery of gastrointestinal motility. The overall treatment effect (for each nosology) in patients with biliary sludge and irritable bowel syndrome using the complex therapy (UDCA and mebeverin) was 84 and 87.8% respectively.Conclusions. Both options are rational today: 1st requires further study; 2nd – active use. Both options exclude polypharmacy and other adverse effects.

Atherosclerotic cardiovascular risk and simulation of lipid-lowering therapy in China

Abstract Background Lipid-lowering therapy is a key strategy to reduce atherosclerotic cardiovascular disease (ASCVD) risk. However, little is known about the burden of lipid-lowering therapy in China. Purpose We aim to simulate the proportion of individuals in need of different lipid-lowering therapy regimens to reach diverse low-density lipoprotein cholesterol (LDL-C) goals based on the ASCVD risk stratification. Methods We used the data from China PEACE Million Persons Project, a national screening project covering 31 provinces in China. The ASCVD risk stratifications and LDL-C goals were based on the 2016 Chinese Guideline for the Management of Dyslipidemia in Adults. Stepwise lipid-lowering therapy (atorvastatin 20 mg, add-on ezetimibe and add-on evolocumab) was simulated by a Monte Carlo model based on individual's LDL-C level. Results We included 2,876,272 participants (89.7% of the screened) who were not receiving lipid-lowering therapy (mean age 55.8±9.9 years; 60.5% women). The proportion of participants at low, moderate, high and very high ASCVD risk were 57.9%, 17.5%, 22.3% and 2.3%, respectively. In individuals at low or moderate risk, 10.5% did not reach the goal of LDL-C&amp;lt;3.4mmol/L; after statin simulation, 99.8% met the goal. In high-risk patients, 49.0% did not reach LDL-C&amp;lt;2.6mmol/L; after statin monotherapy (82.7%), add-on ezetimibe (10.6%) and add-on evolocumab (6.7%), 99.7% met the goal. In very-high-risk patients, 72.2% did not reach LDL-C&amp;lt;1.8mmol/L; while 99.1% met the goal after all patients received the simulation: statin monotherapy (76.5%), add-on ezetimibe (13.0%) and add-on evolocumab (10.5%). In a total of 609,489 participants (21.2% of the overall participants) needing lipid-lowering therapy, 88.5% required statin monotherapy and 11.5% additional non-statin therapy (Figure). Conclusions Moderate-intensity statin therapy is pivotal in the lipid-lowering therapy in China; nearly 10% in need of lipid-lowering therapy required additional non-statin therapy. Funding Acknowledgement Type of funding sources: None.

A case report on long segment hirschprung’s disease

Hirschsprung disease is a complex congenital condition of the intestine, usually recognized to be genetic origin and reverberates from a disturbance of the normal development of the enteric nervous system. It is evident to be the most common cause of a low intestinal obstruction in the neonates as well as the older children. Study reveals that occurrence rate of cases in 70% may be associated with other congenital abnormalities together with number of syndromic phenotypes. A number of distinct genetic sites have been identified in these syndromic phenotypes, identifying potential genetic predispositions. Presenting hereby a case of neonatal hirschsprung’s disease whereby the patient was surgically corrected along with stepwise pharmacological therapy and was able to get discharged with regular follow up advice.

Summary of the 2020 focused updates to U.S. asthma management guidelines: What has changed and what hasn't?

Despite the availability of effective medications, the majority of pediatric and adult patients with persistent asthma have uncontrolled symptoms. This has been attributed to patient nonadherence and poor self-management, but clinicians also contribute through inaccurate assessment of asthma and lack of familiarity with best practice guidelines for medication management. Thus, improving patient outcomes will require improving clinical management by health care providers, including utilization of evidence-based practice guidelines. In this report, we briefly summarize key points of the national guidelines for asthma management and delineate important changes enacted by 2020 Expert Panel Report-4 updates. These include revised recommendations on the use of fractional exhaled nitric oxide testing, indoor allergen mitigation, bronchial thermoplasty, adjunctive immunotherapy, and important modifications to medication management that are likely to have widespread impact on prescribing throughout the United States. In particular, for all patients aged five years and older taking stepwise therapy levels 3-4, it is now recommended to use Single Maintenance and Reliever Therapy, whereas the use of intermittent inhaled corticosteroids (ICSs) administered at the same time as short-acting beta agonist is recommended for step 2 to reduce symptom burden, improve control, and minimize total ICS dose.

Effect of FLT3-ITD Length on 32D Cell Proliferation, Apoptosis and Sensitivity to FLT3 Inhibitor

To study the effects of FLT3-ITD length on 32D cell proliferation, apoptosis and sensitivity to FLT3 inhibitor, so as to provide references for stepwise therapy of FLT3-ITD mutated acute myeloid leukemia patients. Three different FLT3-ITD mutants with same or adjacent insert sites were selected and constructed in an eukaryotic expression vector. FLT3-ITD mutants stably expressed 32D cell strains were selected with the help of lentivirus system and IL3 free cell culture medium. The proliferation and apoptosis of 32D cell strains after AC220 treatment were detected. FLT3-ITD mutants (ITD1, ITD2 and ITD3) stably expressed 32D cell strains were constructed successfully. In the absence of IL3 factor, the proliferation number of ITD1, ITD2 and ITD3 cell strains were mounted up to 2.3 folds, 3.7 folds, and 4.3 folds after 48 hours, respectively. Under the exposure of FLT3 inhibitor AC220, the IC50 values was 0.183, 0.446 and 0.836 nmol/L, and apoptosis rates was 88.6%, 34.2% and 16.1%, respectively. FLT3-ITD mutant expressed cell strains with longer ITD show higher capacity of proliferation and higher tolerance to AC220 treatment.

Approach to Pediatric Intractable Migraine.

Intractable migraine in children and adolescents is a significant cause of disability and decreased quality of life (QoL) in this population. Challenges include lack of unifying definition for intractable migraine, and limited data on best-practice management in this age group, with most current treatment pathways extrapolated from adult studies or expert consensus. A comprehensive approach in the evaluation and management of intractable migraine in this age group encompasses excluding secondary causes of headache; making an accurate diagnosis; identifying and appropriately managing modifiable risk factors; and initiating appropriate pharmacologic therapy to reduce disability, improve health-related quality of life, reduce risk of progression, and develop adaptive pain coping strategies. Several strategies for management of pediatric intractable migraine including use of acute medications, bridge therapy in outpatient setting, emerging therapies for preventive therapy, and a stepwise combination therapy for management of pediatric intractable migraine in emergency and inpatient setting are presented based on available clinical data, safety/tolerability, availability, cost-effectiveness, and expert consensus. This descriptive review of the available literature focuses on approach to therapy for acute intractable migraine in a pediatric population including outpatient, emergency department (ED), and inpatient management.

Insulin secretion is a strong predictor for need of insulin therapy in patients with new-onset diabetes and HbA1c of more than 10%: A post hoc analysis of the EDICT study.

To identify predictors of response to glucose-lowering therapy in patients with new-onset diabetes and very high HbA1c (>10%). The study included EDICT participants with an initial HbA1c of more than 10% (N = 104). All subjects received a 75-g oral glucose tolerance test (OGTT) before initiation of therapy, and then were randomized to receive: (a) initial triple therapy with metformin, pioglitazone and exenatide versus (b) stepwise conventional therapy with metformin followed by glipizide and then glargine insulin to reduce HbA1c to less than 6.5%. Insulin secretion and insulin resistance were calculated with OGTT-derived indices. Sixty-one per cent of participants in the conventional therapy group achieved HbA1c of less than 6.5% at 6 months without need of insulin therapy compared with 78% in the triple therapy group (P = NS). Insulin secretion at baseline was the strongest predictor of subjects who did not require insulin therapy; a cut point of CPEP120 /CPEP0 -the ratio between plasma C-peptide concentration at 120 minutes during the OGTT and fasting plasma C-peptide concentration-of more than 1.7 predicted subjects who achieved the treatment target without insulin, irrespective of the fasting plasma glucose (FPG) concentration and whether or not they were started on conventional or triple therapy. Subjects with a CPEP120 /CPEP0 of less than 1.7 plus FPG of 269 mg/dL or less (≤14.9 mmoL/L) also achieved the treatment goal with triple therapy. Insulin secretion in response to a 75-g OGTT predicts the need for insulin therapy at the time of type 2 diabetes (T2D) diagnosis. A cut point of 1.7 of CPEP120 /CPEP0 provides a useful clinical tool to individualize glucose-lowering therapy in patients with new-onset T2D and HbA1c of more than 10%.

Current situation and prospect of traditional Chinese medicine and western medicine in diagnosis and treatment of failed back surgery syndrome

As a common postoperative complication of lumbar diseases such as lumbar disc herniation, lumbar spinal stenosis and lumbar spondylolisthesis, failed back surgery syndrome(FBSS) seriously affects the postoperative satisfaction of patients due to its difficulty in treatment and long course. At present, the treatment mainly involves comprehensive treatment of traditional Chinese medicine and western medicine, individualized treatment and stepwise therapy. The difficulty lies in how to accurately select the indications and timing of revision surgery, minimizing the damage the spinal stability, and effectively improving the symptoms. In the future, there will be a trend towards precision, minimally invasive, individualized and multidisciplinary therapies. Combined with literature review, the authors summarized the background of FBSS and the status of diagnosis as well as treatment of traditional Chinese medicine and western medicine, and looked forward to the future treatment direction, so as to provide certain reference for clinical treatment of this disease.

Endoscopic Repair of the Proximal Hamstring

Background: Proximal hamstring injuries are increasingly common. While open repair with suture anchors placed in the ischial tuberosity has long been the gold standard technique for surgical management, endoscopic techniques can allow for smaller incisions, reduced wound complications, and an expedited recovery. Indications: Patients with full-thickness 3-tendon proximal hamstring tears, 2-tendon tears with retraction &gt;2 cm, or partial tears that remain symptomatic despite conservative management are considered for surgery. High-demand patients are often treated acutely, and low-demand patients may be offered surgery after a conservative management period. Technique Description: In the prone position, 2 arthroscopic portals are created in the gluteal fold. Fluoroscopy is used to verify safe portal placement, and the sciatic nerve is visualized along with the retracted tendon origin. The ischial tuberosity is identified, and the hamstring origin is debrided and decorticated. An accessory portal is created for suture anchor placement. Two double-loaded anchors are placed in the tuberosity, the sutures of which are used to repair the hamstring tendons using a horizontal mattress configuration. Patients undergo a stepwise postoperative physical therapy protocol. Results: An 85% return to sport rate can be expected following all hamstring repairs, with some studies reporting as high as 95% after endoscopic repair. Compared with nonoperative treatment, proximal hamstring repair overall results in higher patient satisfaction and return to sport. While large studies have yet to report on outcomes compared with the traditional open technique, the smaller incisions look to reduce wound complications and postoperative pain. Discussion/Conclusion: Recent advancements in endoscopic techniques have allowed for adequate visualization and robust repair of proximal hamstring avulsions. We present our endoscopic technique of the proximal hamstring, which, compared with the traditional open repair, can decrease perioperative complications and accelerate recovery.

Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT.

To compare the long-term efficacy of initiating therapy with metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes mellitus (T2DM) versus sequential addition of metformin followed by glipizide and insulin. Drug-naive patients (N = 318) with new-onset T2DM were randomly assigned to receive for 3 years either 1) combination therapy with metformin, pioglitazone, and exenatide (triple therapy) or 2) sequential addition of metformin followed by glipizide and insulin (conventional therapy) to maintain HbA1c at <6.5% (48 mmol/mol). Insulin sensitivity and β-cell function were measured at baseline and 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years. Baseline HbA1c ± SEM values were 9.0% ± 0.2% and 8.9% ± 0.2% in the triple therapy and conventional therapy groups, respectively. The decrease in HbA1c resulting from triple therapy was greater at 6 months than that produced by conventional therapy (0.30% [95% CI 0.21-0.39]; P = 0.001), and the HbA1c reduction was maintained at 3 years in patients receiving triple therapy compared with conventional therapy (6.4% ± 0.1% and 6.9% ± 0.1%, respectively), despite intensification of antihyperglycemic therapy in the latter. Thus, the difference in HbA1c between the two treatment groups at 3 years was 0.50% (95% CI 0.39-0.61; P < 0.0001). Triple therapy produced a threefold increase in insulin sensitivity and 30-fold increase in β-cell function. In conventional therapy, insulin sensitivity did not change and β-cell function increased by only 34% (both P < 0.0001 vs. triple therapy). Triple therapy with agents that improve insulin sensitivity and β-cell function in patients with new-onset T2DM produces greater, more durable HbA1c reduction than agents that lower glucose levels without correcting the underlying metabolic defects.

Basic principles for the treatment of chronic rhinosinusitis with nasal polyps

Introduction. Chronic rhinosinusitis with nasal polyps (CRSwNP) is based on a chronic inflammatory hyperplastic process in the mucosa membrane of the nasal cavity and paranasal sinuses (SNPs). According to the consensus on the biological treatment of CRSwNP with or without asthma, which is one of the latest consensus documents of the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), which was published in December 2019, the need for surgical treatment or systemic administration of corticosteroids due to the active nasal polyps growth are conditional signs for the decompensation of clinical control. Currently, the basic treatment for patients with CRSwNP is the long-term use of intranasal corticosteroids (INCS), which leads to an improvement in the quality of life, while minimizing the risk of exacerbations and complications.Research purpose. To evaluate the effectiveness of the basic therapy of intranasal glucocorticosteroid mometasone furoate for different phenotypes of CRSwNP.Methods. All patients with recurrent CRSwNP were divided into 3 equal phenotypic groups of 40 people each: group 1 – CRSwNP without asthma and respiratory allergies, group 2 – CRSwNP + atopy, group 3 – CRSwNP + non-allergic asthma. The observation period was 3 years.Results. Using the algorithm of stepwise therapy of CRSwNP, dynamic monitoring of these patients by an ENT and an allergistimmunologist, basic therapy with corticosteroids with constant treatment correction once every 3 months, it was possible to stabilize the inflammatory process throughout the respiratory tract and reduce the need for surgical treatment.Conclusion. With CRSwNP, long-term use of Mometasone furoate INCS is the main drug of basic therapy to minimize the recurrence of nasal polyp growth and is accompanied by clinical efficacy and the absence of adverse side effects.

Supplemental oxygen therapy in COVID-19

South Africa face a significant shortage of ventilator-supported intensive care (ICU) beds during the peak phase of the COVID-19 pandemic, further exacerbated by severe ICU-staff shortages. It is also recognised that the mortality rate for ventilated patients might be as high as 88%. In the absence of a vaccine and proven effective pharmacotherapy, it is important to understand the pathophysiological processes causing progression. Early type-L COVID-19, associated with pulmonary thrombo-embolism, may be amenable to treatment with careful anti-coagulation and supplementary oxygenation strategies. This could attenuate the severe hyperventilation phase causing patient self-inflicted lung injury (P-SILI) that contributes to the development of type-H COVID-19 pneumonia. Type-H is an ARDS variant requiring intubation and ventilation and is associated with a very high mortality rate. Stepwise non-invasive positive pressure ventilation strategies (NIPPV) providing supplementary oxygen have shown benefit and, in the South African context, may be the only realistic strategy to deal with high numbers of patients during the early type-L phase of the disease. To address this, a mobile wall unit has been created that allows for stepwise supplementary oxygen therapy according to protocol – including NIPPV as well as standard ventilation. The unit can support modified wards, field hospitals or high care areas in existing facilities. It allows for NIPPV support within a hood system linked to scavenger lines addressing aerolisation. Standard humidification, flow regulators, vacuum systems, HFNC and CPAP systems, as well as monitoring equipment that are readily available in South Africa, can be linked to the system addressing availability issues.

Factors Associated with Failure of Intermittent Nebulization with Short-Acting Beta-Agonists in Children with Severe Asthma Exacerbation.

PurposeIntermittent nebulization of short-acting beta-agonists (SABA) is the initial treatment of choice for children with asthma exacerbation. However, children with severe asthma exacerbation (SAE) may not show an adequate response and need aggressive stepwise therapy. We aimed to explore factors associated with a poor response to intermittent nebulized SABA in children with SAE.MethodsA retrospective cohort study of children with SAE diagnosed according to the definition of the British Guidelines on the Management of Asthma, who were admitted at Hat Yai Hospital from January 1, 2015, to December 31, 2017. All children were treated with intermittent SABA nebulization. Treatment failure was defined as children needing escalated therapy. Logistic regression with confounding score adjustment was used to explore the predictors of treatment failure.ResultsOne hundred thirty-three children were included in the analysis, 59 were in the failure group and 74 were in the success group. After adjusting for potential confounders, they were significantly associated with a previous history of intubation (adjusted OR 6.46, 95% CI 1.13 to 36.79, p=0.036), receiving <3 doses of nebulized salbutamol in the emergency room (ER, aOR 3.21, 95% CI 1.15 to 9.02, p=0.027), ER measured oxygen saturation (SpO2) <92% (adjusted OR 3.02, 95% CI 1.18 to 7.75, p=0.022), and exacerbation triggered by pneumonia (adjusted OR 2.67, 95% CI 1.19 to 6.00, p=0.017).ConclusionWe identified four prognostic factors of treatment failure in children with SAE: a previous history of intubation; receiving <3 doses of nebulized salbutamol in the ER, SpO2 at ER <92%; and exacerbation triggered by pneumonia. Further prospective studies are required to confirm our findings before clinical implementation.

Efficacy of Chinese Children's Asthma Action Plan in the management of children with asthma.

Background: Abundant evidence has proven the effectiveness of following an asthma action plan for children. China released its first children's asthma action plan in 2017 to improve asthma control. Objective: To assess the effectiveness of the Chinese Children's Asthma Action Plan (CCAAP) in the management of children with asthma. Methods: Children with persistent asthma (6-14 years old) at 10 tertiary hospitals were randomized to receive either CCAAP instructions (intervention group, n = 87) or no plan (control group, n = 86) in addition to the usual asthma care, including education, stepwise asthma therapy, and regular outpatient follow-up. Children were followed up by using a serial measurement of outcomes over the course of 3 months. Results: CCAAP instructions did not have a significant effect on any of outcomes compared with the intervention group: (1) variables related to asthma exacerbation, including the number of patients (p = 0.09), symptomatic days (p = 0.658), severity, medication (courses of reliever, p = 0.696; combined rhinitis medication, p = 0.081; combined oral antibiotics, p = 0.852), missed work days (p = 0.538) or school days (p = 0.441), and economic costs (p = 0.898); (2) asthma control (p = 0.180); or (3) pulmonary function parameters during the follow-up period. Both groups showed significant improvement in asthma control (both p < 0.001) and pulmonary function (p < 0.017) from baseline to the 3-month follow-up. Conclusion: The results of this study indicated that provision of CCAAP may play a useful role in the management of children with asthma, but there were no greater benefits than usual asthma care. We need to plan a larger appropriately powered study.